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Clinical nursing
Compliance of oral nutritional supplements in postoperative patients with digestive tract cancer:an analysis based on COM-B model
SU Liqing, ZHANG Jie, DOU Wenyue, LI Mengxue, ZHANG Yumeng, CHANG Jian
2024, 44 (10):  1213-1220. 
doi: 10.3969/j.issn.1674-8115.2024.10.001

Abstract ( 53 )   HTML ( 2 )   PDF (1574KB) ( 37 )  

Objective ·To explore the influencing factors of oral nutritional supplement compliance in postoperative patients with digestive tract cancer based on COM-B model, and to analyze the mediating role of medication belief and self-efficacy in oral nutritional supplement. Methods ·A total of 300 postoperative gastrointestinal cancer patients were selected by convenience sampling method. The General Information Questionnaire, Morisky Medication Adherence Scale, Digestive Cancer Patients Nutrition Knowledge, Attitude and Practice Questionnaire, Multidimensional Scale of Perceived Social Support, Beliefs about Medicines Questionnaire and General Self-Efficacy Scale were used. A mediating effect model was used to analyze the influencing factors of compliance with oral nutritional supplements. Results ·The score of Morisky Medication Adherence scale was 1.61±1.38, which was at a low level. Oral nutritional supplement compliance was significantly positively correlated with nutrition knowledge, social support, medication belief and self-efficacy (r=0.391, 0.401, 0.438, 0.410, all P<0.01). Medication belief had a partial mediating effect between nutrition knowledge and adherence to oral nutritional supplements (effect size =0.097, accounting for 18.00% of the total effect). Self-efficacy had a partial mediating effect between nutrition knowledge and oral nutritional supplement compliance (effect size =0.044, accounting for 8.16% of the total effect). Self-efficacy had a partial mediating effect between social support and oral nutritional supplement compliance (effect size =0.044, accounting for 16.67% of the total effect). Conclusion ·The compliance of oral nutritional supplements in postoperative patients with gastrointestinal cancer is at a low level. The individualized nursing intervention can increase the nutritional knowledge of patients, improve the social support, reduce the concerns of patients about oral nutrition, and improve the self-efficacy of patients, so as to promote the compliance of patients with oral nutritional supplements.

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Application of online courses combined with teach-back method to laryngectomy patients and family carers
HUANG Jialu, LI Shan, ZHANG Caiyun, XU Fei
2024, 44 (10):  1221-1228. 
doi: 10.3969/j.issn.1674-8115.2024.10.002

Abstract ( 55 )   HTML ( 3 )   PDF (1389KB) ( 22 )  

Objective ·To explore the effect of online courses combined with the teach-back method among patients with laryngectomy and their family caregivers. Methods ·Convenience sampling was used to select patients with laryngectomy treated in the Department of Otolaryngology, Shanghai Changhai Hospital from July 2022 to June 2023 and their family caregivers. The participants were divided into a control group and an observation group using the random number table method. The intervention was conducted in two different wards. General information of the two groups of patients and caregivers was collected. After admission, the control group watched offline videos recorded by the department. The videos introduced laryngocarcinoma-related knowledge and standard procedures of airway stoma care, suctioning, nasal feeding, etc., which were divided into 4 sessions with 30 min each. The patients watched one session per week. The observation group watched the same videos (8 lessons) online on their own after admission, while the nursing staff used the teach-back method for health education, consolidating 2 lessons once a week, 45 min/session for 4 weeks. The effectiveness of the intervention was evaluated by using Caregiver Preparedness Scale (CPS), Family Caregiver Task Inventory (FCTI), and Chinese Quality of Life Instruments for Cancer Patients-Head and Neck Cancer (QLICP-HN) at baseline (1st week), before discharge (4th week), and one month after discharge (8th week), as well as the incidence of adverse events during home care. Results ·The study included a total of 120 pairs of patients and caregivers, with 60 pairs in each group. Five pairs in each group were excluded due to various reasons, leaving a total of 55 pairs in each group. There were no statistically significant differences between the two groups in terms of general information of the patients and the caregivers, QLICP-HN scores of the patients, and CPS and FCTI scores of the caregivers at baseline (P>0.05). Before discharge and 1 month after discharge, the CPS scores of the caregivers and the QLICP-HN scores of the patients in the observation group were significantly higher than those in the control group, and the FCTI scores were significantly lower (lower scores indicating better nursing care), with statistically significant differences (P<0.05). Within 1 month after discharge, the incidence of adverse home care events in the observation group was lower than that in the control group (5.5% vs 29.1%), and the difference was statistically significant (P<0.05). Conclusion ·The online courses combined with the teach-back method help improve the readiness to care and caregiving competence of family caregivers of post-laryngectomy patients, improve patients' quality of life, and reduce the incidence of adverse events during home care.

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Effect of prehospital multimodal prehabilitation on preoperative function and postoperative recovery in patients with gastrointestinal malignant tumors
TAI Rui, SUN Jufang, LIN Ying, ZHANG Yaqing, HUANG Chen, FANG Fang
2024, 44 (10):  1229-1234. 
doi: 10.3969/j.issn.1674-8115.2024.10.003

Abstract ( 37 )   HTML ( 3 )   PDF (1303KB) ( 22 )  

Objective ·To explore the effect of a prehospital multimodal prehabilitation program on the preoperative functional status and postoperative recovery of patients with gastrointestinal malignant tumors. Methods ·A total of 78 patients with gastrointestinal malignant tumors, hospitalized in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from June to December 2023, were enrolled. They were divided into the standard group (SD group, n=40) and the prehospital multimodal prehabilitation group (PMP group, n=38) by using random number table. From the time the operation was agreed upon by both the doctor and patient to the day before the operation, the SD group followed the routine preoperative guidance, while the PMP group received a home-based prehospital multimodal prehabilitation program. The general data of patients were collected, and the six-minute walk distance (6MWD) was compared between the two groups at baseline and on the day before operation.The length of postoperative hospitalization, time to first flatus, time to first ambulation, time to first oral intake, drainage removal time and postoperative complication rate were also compared between the two groups. Results ·There was no difference in general data and duration of preoperative intervention of patients between the two groups. At baseline, there was no significant difference in 6MWD between the two groups. On the day before operation, the 6MWD in the PMP group was higher than that in the SD group (P= 0.016). Changes in 6MWD in the PMP group were significantly higher compared to SD group during the preoperative period, with values of (23.42±13.59) m vs. (-3.75±12.08) m (P<0.001). Time to first flatus, time to first ambulation and time to first oral intake in the PMP group were earlier than those in the SD group (P<0.05). However, there was no significant difference in drainage removal time, postoperative hospitalization and postoperative complication rate between the two groups (P>0.05). Conclusion ·Prehospital multimodal prehabilitation can improve the preoperative function and accelerate the postoperative recovery in patients with gastrointestinal malignancies.

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Effect of early goal-directed activity on gastrointestinal function recovery after pancreatic surgery
YAO Hui, ZHANG Yun, DAI Chenjun, GAO Wenqing, YAO Wenjie, DUAN Xiaolei, YANG Fu
2024, 44 (10):  1235-1240. 
doi: 10.3969/j.issn.1674-8115.2024.10.004

Abstract ( 31 )   HTML ( 3 )   PDF (1300KB) ( 25 )  

Objective ·To investigate the safety and feasibility of early goal-directed mobilization in the recovery of gastrointestinal function after pancreaticoduodenectomy. Methods ·The non-contemporaneous controlled studies were conducted. Subjects who underwent pancreaticoduodenectomy were included. From Sep 2022 to May 2023, forty patients were selected as the control group, and forty patients were selected from June 2023 to February 2024 as the experimental group. The general clinical data of the two groups were collected. The control group was treated with the nursing routine after pancreaticoduodenectomy, and there were no specific requirements for the time and goal of early activity. The experimental group had daily activity goals established for early mobilization, which were performed by the patients and their families, while the rest of their care was identical to that of the control group. The main index of effectiveness evaluation was the time of first flatus and first defecation, and the secondary indexes included the time of first getting out of bed, the time of oral drinking, the time of the gastric tube removal, and the postoperative levels of K+, Na+, and Cl- on the 3rd day of the postoperative period. Safety evaluations included chyle leak, postoperative pancreatic fistula, biliary leak and delayed gastric emptying, postoperative hemorrhage, unplanned reoperation, unplanned extubation, falls and death. Results ·There was no statistically significant difference in the general clinical data of the patients in the 2 groups. After the implementation of early goal-directed mobilization, the time of first flatus was advanced from (3.95±1.68) d to (2.88±0.91) d (t=-3.560, P=0.001), and the time of first defecation was advanced from (4.90±1.61) d to (3.80±1.30) d (t=-3.352, P=0.001). The time of first getting out of bed was advanced from (5.18±1.77) d to (2.30±0.88) d (t=-9.205, P<0.001), and the time of oral drinking was advanced from (4.10±1.89) d to (2.73±1.20) d (t=-3.883, P<0.001). Significant differences were also observed in postoperative day 3 Na+ (t=-2.745, P=0.008) and Cl- (t=-2.033, P=0.045) levels. Conclusion ·Early goal-directed activity programs are safe and effective in promoting the recovery of gastrointestinal function after pancreaticoduodenectomy.

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Basic research
miR-128-3p inhibits the proliferation of keratinocytes in psoriasis via repressing leptin
PENG Jing, YIN Jing, XIA Ping, CHEN Liuqing
2024, 44 (10):  1241-1248. 
doi: 10.3969/j.issn.1674-8115.2024.10.005

Abstract ( 52 )   HTML ( 3 )   PDF (3550KB) ( 19 )  

Objective ·To explore the role of miR-128-3p/leptin (LEP) axis in the proliferation and inflammation of keratinocytes in psoriasis. Methods ·BALB/c mice were randomly divided into a control group (n=10) and a model group (n=10). Mice in the model group were given imiquimod on the back. miR-128-3p overexpression and interference plasmids, as well as LEP interference plasmids, were constructed and transfected into HaCaT cells, respectively. miR-128-3p and LEP mRNA were quantified by real-time quantitative polymerase chain reaction, and LEPprotein levels were detected by using Western blotting. Enzyme-linked immunosorbent assay was used to measure the content of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the culture medium. MTT assay was used to evaluate cell activity and EdU assay was to used to test cell proliferation. The binding site between miR-128-3p and LEP was determined by using a dual luciferase reporter gene assay. Results ·Compared with mice in the control group, mice in the model group showed downregulated expression of miR-128-3p and upregulated expression of LEP at both RNA and protein levels (all P<0.05). The dual luciferase reporter gene assay confirmed that LEP was a downstream target of miR-128-3p. Compared with the negative control mimic (NC mimic) group, expression of miR-128-3p was up-regulated in the miR-128-3p mimic group, and expression of LEP was reduced. The levles of TNF-α, IL-6, and IL-1β were significantly lower in the miR-128-3p mimic group than in the NC mimic group. The relative cell viability and EdU-positive cell rate were also reduced after miR-128-3p up-regulation (all P<0.05). Compared with the negative control inhibitor (NC inhibitor) group, expression of miR-128-3p was down-regulated in the miR-128-3p inhibitor group, and expression of LEP was increased. The levles of TNF-α, IL-1β and IL-6 were increased after miR-128-3pdownregulation. miR-128-3p down-regulation led to an increase in relative cell viability and EdU-positive cell rate (all P<0.05). Further experimental results showed that LEP expression was up-regulated in the miR-128-3p inhibitor+LEP inhibitor group compared with that in the LEP inhibitor group, whereas the levels of TNF-α, IL-6, and IL-1β were elevated, and the relative viability of the cells and the rate of EdU-positive cells were increased (all P<0.05). Conclusion ·miR-128-3p downregulates LEP to inhibit the proliferation and inflammatory response of keratinocytes, thereby inhibiting the occurrence and development of psoriasis.

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Expression of miR-146a in CD4+ T lymphocytes of patients with rheumatoid arthritis and its correlation with inflammatory cytokines
LI Bo, HU Qiuxia, WU Ximei, SHE Ruonan, TAN Jinhui, LUO Junjia, YANG Haitao, ZHANG Haoru
2024, 44 (10):  1249-1254. 
doi: 10.3969/j.issn.1674-8115.2024.10.006

Abstract ( 35 )   HTML ( 3 )   PDF (1423KB) ( 16 )  

Objective ·To investigate the expression of miR-146a in peripheral blood CD4+ T lymphocytes of patients with rheumatoid arthritis (RA) and its correlation with inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Methods ·A total of 30 active RA patients who received medical treatment and 30 healthy controls who underwent physical examinations at the People's Hospital of Longhua, Shenzhen from August 2019 to July 2021 were selected. Peripheral blood mononuclear cells (PBMCs) and CD4+ T lymphocytes were isolated from venous blood extracted from RA patients and healthy controls, respectively. Quantitative real-time PCR (qPCR) was used to detect the expression of miR-146a in peripheral blood CD4+ T lymphocytes, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of TNF-α and IL-6. After transfection of the peripheral blood CD4+ T lymphocytes of RA patients with miR-146a mimic, the expression of miR-146a, TNF-α and IL-6 was detected again. The correlations between miR-146a expression and TNF-α and IL-6 expression in RA patients, both before and after transfection, were analyzed by using Pearson correlation coefficient. Results ·Before transfection with miR-146a mimic, the expression levels of miR-146a, TNF-α and IL-6 in peripheral blood CD4+ T lymphocytes of RA patients were significantly higher than those of healthy controls (all P<0.001). After transfection, the expression of miR-146a in peripheral blood CD4+ T lymphocytes of RA patients was significantly higher, and the expression of TNF-α and IL-6 was significantly lower (all P<0.001). The results of Pearson correlation analysis showed that the expression of miR-146a in peripheral blood CD4+ T lymphocytes of RA patients, both before and after transfection, was positively correlated with the expression of TNF-α and IL-6, respectively (r=0.959, P<0.001; r=0.916, P<0.001; r=0.971, P<0.001; r=0.861, P<0.001). Conclusion ·miR-146a can regulate the levels of TNF-α and IL-6 in peripheral blood CD4+ T lymphocytes of RA patients, indicating that miR-146a may play a role in the pathogenesis of RA.

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Mechanistic study on the promotion of pancreatic cancer progression through upregulation of ZNF143 by dysregulated fatty acid metabolism
YU Siwei, XU Ziqi, TAO Mengyu, FAN Guangjian
2024, 44 (10):  1255-1265. 
doi: 10.3969/j.issn.1674-8115.2024.10.007

Abstract ( 40 )   HTML ( 5 )   PDF (8407KB) ( 20 )  

Objective ·To identify key genes that may be regulated by fatty acid alteration in pancreatic cancer through tumor transcriptome screening, and to explore the expression of zinc finger protein 143 (ZNF143) in pancreatic cancer and its effect on the migration and invasion of pancreatic cancer cells. Methods ·The R language was utilized to integrate transcriptome data, including the GSE164760 dataset from the Gene Expression Omnibus (GEO) database, 179 pancreatic cancer tissue samples and 4 adjacent non-cancerous tissue samples from The Cancer Genome Atlas (TCGA) database, as well as 167 normal pancreatic tissue samples from the Genotype-Tissue Expression (GTEx) database. We conducted screening and analysis of potential differential genes that may be induced by dysregulation of fatty acid metabolism in pancreatic cancer. After treating pancreatic cancer cells with palmitic acid (PA) and oleic acid (OA) for 24 hours, the mRNA levels of candidate genes were detected by qRT-PCR. According to the median expression level of the screened gene, pancreatic cancer patients in the TCGA database were divided into two groups with high and low expression of ZNF143. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were performed for the differential genes of the two groups. siRNA was used to knock down the expression of ZNF143 in pancreatic cancer cells, and the effects on cell migration and invasion were examined by wound healing assay and invasion assay. Western blotting was used to explore the impact of ZNF143 on epithelial mesenchymal transition (EMT)-related proteins and the Wnt/β-catenin pathway. Results ·The bioinformatics database was processed to analyze key genes associated with the up-regulation of genes in lipid metabolism disorders in pancreatic cancer and liver cancer. Among them, ZNF143 was a potential gene associated with fatty acid accumulation in pancreatic cancer. In vitro experiments confirmed that the mRNA level of ZNF143 was significantly up-regulated after treating pancreatic cancer cells with palmitic acid or oleic acid. Both KEGG and GO enrichment analyses demonstrated that the differentially expressed genes associated with ZNF143 were predominantly enriched in adhesion pathways. In functional experiments, the migration and invasion abilities of pancreatic cancer cells transfected with ZNF143 siRNA were reduced, and the expression of EMT-related proteins was also decreased, potentially related to the activation of the Wnt/β- catenin pathway. Conclusion ·Fatty acid accumulation up-regulates the mRNA expression of ZNF143 in pancreatic cancer cells, and ZNF143 may enhance the migration and invasion of these cells by facilitating EMT through activation of the Wnt/β-catenin pathway.

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Clinical research
Correlation between serum SUMO1 level and hypertriglyceridemia in type 2 diabetes mellitus patients
ZHANG Xinyan, LI Han, RAN Hui, SU Qing, ZHANG Hongmei
2024, 44 (10):  1266-1272. 
doi: 10.3969/j.issn.1674-8115.2024.10.008

Abstract ( 45 )   HTML ( 2 )   PDF (1361KB) ( 30 )  

Objective ·To explore the correlation between serum small ubiquitin-like modifier 1 (SUMO1) levels and hypertriglyceridemia in patients with type 2 diabetes mellitus (T2DM). Methods ·A total of 239 newly diagnosed T2DM patients were recruited from the endocrinology clinic of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, between September 2020 and March 2021. Among them, 92 patients had hypertriglyceridemia, and 147 patients did not. Basic information and laboratory parameters were collected. The differences in serum SUMO1 levels between the two groups were analyzed. Factors influencing hypertriglyceridemia in patients with T2DM were analyzed, and the impact of serum SUMO1 levels on the risk of hypertriglyceridemia in T2DM patients was investigated. Results ·Patients with T2DM and hypertriglyceridemia had significantly higher serum SUMO1 levels compared to those without hypertriglyceridemia (1 114.99 pg/mL vs 902.43 pg/mL, P<0.001). Binary Logistic regression analysis suggested that serum SUMO1 levels (OR=1.527, 95%CI 1.200?1.943), glycated hemoglobin (OR=1.202, 95%CI 1.038?1.391), and blood uric acid (OR=1.006, 95%CI 1.003?1.010) were independent risk factors for hypertriglyceridemia in patients with T2DM. After adjusting for various confounding factors and stratifying serum SUMO1 levels into quartiles, the risk of hypertriglyceridemia in T2DM patients with the highest quartile (Q4) of serum SUMO1 levels was 2.707 times higher compared to those in the lowest quartile (Q1) (95%CI 1.231?5.951). Multiple linear stepwise regression analysis revealed that female gender, waist-to-hip ratio, triglycerides and serum creatinine were independent risk factors for elevated serum SUMO1 levels. Conclusion ·Serum SUMO1 level in patients with T2DM complicated with HTG is significantly higher than that in patients without HTG, and the serum SUMO1 level is an independent risk factor for T2DM complicated with HTG.

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Age-related changes of alveolar bone in maxillary posterior based on cone-beam CT
ZHAO Meng, JIANG Liting, GAO Yiming
2024, 44 (10):  1273-1278. 
doi: 10.3969/j.issn.1674-8115.2024.10.009

Abstract ( 37 )   HTML ( 0 )   PDF (2519KB) ( 15 )  

Objective ·To measure and analyze age-related changes in cortical bone thickness and alveolar bone height and width in the posterior teeth of the maxilla. Methods ·Cone-beam CT (CBCT) data of the implant patients in the Department of Stomatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were collected from January 2019 to December 2022. There were 40 cases in the youth group (18?30 years) and 40 cases in the elderly group (≥60 years), with a male-to-female ratio of 1∶1. The i-Dixel software was used to measure the thickness of buccal and palatal cortical bone, and the width and height of alveolar bone in three regions of the posterior teeth of the maxilla on the side with regular dentition (part Ⅰ: between the first and the second premolar of maxillary; part Ⅱ: between the second premolar and the first molar of maxillary; part Ⅲ: between the first and the second molar of maxillary), and the differences between different groups were compared. Results ·In part Ⅲ, the buccal cortical bone thickness of the elderly men [(1.49±0.29) mm] was significantly greater than that of the young men [(1.11±0.34) mm] (P<0.001). In part Ⅰ and Ⅱ, the thickness of palatal cortical bone in the elderly women [part Ⅰ: (1.27±0.30) mm; part Ⅱ: (1.28±0.27) mm] was significantly smaller than that in the young women [part Ⅰ: (1.70±0.32) mm; part Ⅱ: (1.58±0.61) mm] (P<0.05). The width of alveolar bone showed a trend of being smaller in the elderly group than in the young group in all three regions, but there were significant differences only between the elderly males [part Ⅱ: (8.61±1.15) mm; part Ⅲ: (11.06±2.40) mm] and the young males [part Ⅱ: (10.29±1.69) mm; part Ⅲ: (13.39±1.59) mm] in the part Ⅱ and Ⅲ (P<0.05). The alveolar bone height in part Ⅰ and Ⅱ was significantly greater in elderly men and women than that in the young men and women, respectively (P<0.05). In the elderly group, the thickness of buccal cortical bone in men was significantly greater than that in women in part Ⅰ and Ⅲ (P<0.05). Conclusion ·The thickness of palatal cortical bone in female maxillary posterior teeth significantly decreases with age; the width of alveolar bone in maxillary posterior region shows a narrowing trend with age, especially in elderly men; the height of alveolar bone in the maxillary posterior region of the elderly increases significantly.

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Techniques and methods
Establishment and verification of auditory brainstem implant vocoder model
ZHANG Qinjie, HUANG Sui, TAN Haoyue, ZHOU Xiang, WANG Junyi, LIU Yuzi, WEN Wen, GUO Jia, WU Hao, JIA Huan
2024, 44 (10):  1279-1286. 
doi: 10.3969/j.issn.1674-8115.2024.10.010

Abstract ( 34 )   HTML ( 2 )   PDF (2849KB) ( 33 )  

Objective ·To develope an auditory brainstem implant (ABI) vocoder based on cochlear implant (CI) vocoder characteristics and ABI electrode array topology, and to verify its reliability. Methods ·An "n-of-m" coding strategy CI/ABI vocoder was constructed based on MATLAB. Within each frame, only the envelopes of the n channels with the highest energy were selected. The interaction coefficient (IC) (range: 1?3), channel numbers (range: 5?22), and electrode array topology (CI/ABI) were adjustable parameters, allowing for the synthesis of simulated speech. Psychoacoustic evaluation was employed, recruiting normal hearing subjects to perform closed-set simulated phoneme perception. The phoneme recognition accuracy (20 vowel questions/condition, 11 consonant questions/condition) was compared with the corresponding conditions of CI and ABI from reference literature to determine the IC value of the vocoder and verify its reliability. Results ·The vocoder successfully synthesized all test stimuli. In the closed-set CI-simulated speech recognition, the simulated vowel and consonant recognition accuracy for IC2 and IC3 conditions showed no significant difference compared to the accuracy reported in the CI reference literature (P>0.05). The difference in vowel and consonant accuracy between IC2 and the literature was smaller than that between IC3 and the literature (vowel |d|=1.6% vs. 20%, consonant |d|=8.4% vs. 9.9%), thus determining the optimal interaction coefficient of this model as 2. Subsequently, when modifying the electrode array topology to ABI, it was found that the simulated phoneme recognition accuracy for a 16-channel ABI was significantly lower than that for the 16-channel CI group, consistent with the reported literature. The simulated vowel and consonant accuracy within the 5?8 channel range for ABI showed no significant difference (P>0.05), also aligning with the trend reported in the literature. Conclusion ·A CI/ABI vocoder based on "n-of-m" coding strategy is established and the optimal IC is determined. The established ABI encoder has been evaluated for high reliability through psychoacoustic experiments. It provides suitable technical means for validating ABI-specific coding strategies.

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Review
Research progress in Menin-MLL interaction and its inhibitors in MLL-rearranged leukemia
FANG Xinyue, SHI Lan, XIA Siyi, WANG Jiaxuan, WU Yingli, HE Kejun
2024, 44 (10):  1287-1298. 
doi: 10.3969/j.issn.1674-8115.2024.10.011

Abstract ( 55 )   HTML ( 1 )   PDF (2449KB) ( 41 )  

Acute leukemias caused by mixed lineage leukemia (MLL) gene rearrangements (MLL-r) are characterized by high invasiveness and a poor prognosis, with few specific treatment options available. MLL protein is essential in embryonic development and hematopoiesis. It exhibits histone methyltransferase activity and can interact with various proteins through its functional domains, thus regulating downstream target gene expression through epigenetic modifications. MLL-r leads to the formation of MLL fusion proteins (MLL-FPs), in which the C-terminal is replaced by fusion partner proteins; over 100 such partner proteins have been identified to date. In numerous studies of the molecular mechanism, Menin serves as an important cofacter in the leukemogenesis of MLL-FPs and participates in forming the key complex when interacting with the N terminal of MLL protein, resulting in the disregulation of certain targeted genes, which makes the development of Menin-MLL inhibitors theoretically possible. To date, several small molecules have been identified that inhibit Menin-MLL interaction, including thienopyrimidine derivatives, piperidine derivatives, pyrimidine derivatives, and macrocyclic mimic peptides. Based on these prototypes, at least seven drugs are currently undergoing clinical evaluation, with some promising preliminary data regarding safety, tolerability, and efficacy. This review summarizes the structure and function of MLL, the mechanism of the occurrence of MLL-r leukemia, and current Menin-MLL inhibitors tested in MLL-r leukemia.

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Research progress in the role of endo cannabinoid system in liver diseases
BIAN Shu, YU Qian, LIU Liangming
2024, 44 (10):  1299-1306. 
doi: 10.3969/j.issn.1674-8115.2024.10.012

Abstract ( 29 )   HTML ( 1 )   PDF (1858KB) ( 33 )  

The endocannabinoid system (ECS) consists of a variety of long-chain unsaturated fatty acid analogs, mainly anandamide (AEA) and 2-arachidoniyl glycerol (2-AG), along with their specific binding G protein-coupled receptors, cannabinoid receptor 1 (CB1R) and cannabinoid receptor 2 (CB2R). It affects the life process and biological activity of almost all cells in the body by influencing cell material and energy metabolism. In the liver, the physiological expression of ECS is at a low level. The expression and secretion of ECS in the liver can be strongly stimulated by liver injury factors. ECS acts as a trigger in multiple liver diseases. It is known to be related to the process of hepatocyte steatosis and promote the formation and development of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). It is involved in the inflammatory processes of liver diseases and greatly affects the immune-inflammatory response in liver tissue. It is also involved in the formation of liver fibers and promotes the occurrence and development of liver fibrosis and cirrhosis. Finally, the role and mechanisms of ECS in the occurrence and development of liver diseases are elaborated in detail by listing lipid metabolism-related liver diseases (NAFLD and ALD) and other liver diseases.

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Progress in mechanisms and treatment of sunitinib resistance in renal cell carcinoma
CHEN Zixuan, LIU Min
2024, 44 (10):  1307-1315. 
doi: 10.3969/j.issn.1674-8115.2024.10.013

Abstract ( 65 )   HTML ( 6 )   PDF (2199KB) ( 31 )  

Renal cell carcinoma (RCC) originates from the epithelial cells of renal tubules and is the most common type of renal cancer, as well as the urological tumor with the highest mortality rate. Over the past half-century, the morbidity and mortality of RCC have been increasing, posing a significant threat to human health. Although surgical treatment offers the possibility of a cure for most RCC patients, tumor recurrence or metastasis leads to the failure of traditional treatment options to achieve the desired results. The advent of targeted drugs, such as receptor tyrosine kinase inhibitors and immune checkpoint inhibitors, has brought new hope for the treatment of RCC. Targeted therapy has become the mainstay of treatment for advanced RCC. Sunitinib is a receptor tyrosine kinase inhibitor that plays a pivotal role in the treatment of RCC. It inhibits the activity of various receptor tyrosine kinases, including epidermal growth factor receptor, platelet-derived growth factor receptor, and vascular endothelial growth factor receptor. This, in turn, inhibits tumor angiogenesis and cellular proliferation, effectively controlling tumor progression. However, a considerable number of RCC patients develop resistance to sunitinib within 15 months of initiating treatment, presenting new challenges for the treatment of RCC. Therefore, this paper summarizes the mechanism of sunitinib resistance in RCC and reviews the treatment of sunitinib resistance in RCC, in order to provide ideas for overcoming the resistance of RCC to sunitinib, and developing a more effective treatment plan for patients with advanced RCC.

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Advances of GADD45b in hepatic glucose and lipid metabolism
WANG Renjie, HUA Hui, ZHU ChaoYu, WEI Li
2024, 44 (10):  1316-1322. 
doi: 10.3969/j.issn.1674-8115.2024.10.014

Abstract ( 45 )   HTML ( 1 )   PDF (2232KB) ( 22 )  

Growth arrest and DNA damage-inducible 45b (GADD45b) was initially discovered to be involved in processes such as cell cycle arrest, differentiation and apoptosis. It is an important signal regulatory molecule in cells, responsible for signal transduction under various physiological or environmental stimuli. The GADD45b gene belongs to the GADD45 gene family. This gene is commonly expressed in human and fetal tissues, but the expression is tissue-specific, with high expression in the liver and bone marrow. The GADD45b protein is a small, evolutionarily conserved acidic protein distributed in both the cytoplasm and nucleus. Research has shown that GADD45b is closely associated with signaling pathways such as p38/MAPK and TGFβ/Smad3, and it has functions including improving tissue fibrosis and inflammation progression, inhibiting cell autophagy, and enhancing neural function recovery. GADD45b plays a significant role in tumors, innate immunity, neurological diseases, and disorders of hepatic glucose and lipid metabolism. The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing year by year in China and has become a serious public health issue in the country. Disorders in hepatic glucose and lipid metabolism are major causes of NAFLD. Multiple studies have shown that GADD45b gene and protein exhibit abnormal expression in liver diseases with hepatic glucose and lipid metabolism disorders. Previous research has found that GADD45b can increase the stability of the FoxO1 protein in hepatocytes, and enhance the expression of PGC1a, thereby promoting hepatic gluconeogenesis. Additionally, GADD45b can inhibit fatty acid transport in hepatocytes by binding to FABP1 and reduce hepatic steatosis by interacting with HSP72 protein. Therefore, the roles of GADD45b in promoting hepatic gluconeogenesis, inhibiting fatty acid transport, and reducing steatosis may form the basis for research into treatments for hepatic glucose and lipid metabolism disorders and liver diseases. This paper reviews the characteristics and functions of the GADD45b protein, as well as recent advances in the study of hepatic glucose and lipid metabolism and liver diseases, aiming to provide reference for further GADD45b research.

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Research progress in the relationship between FOXM1 and neoplasm metabolism
LI Yu, JIANG Yifan, TONG Rongliang, CHEN Diyu, WU Jian
2024, 44 (10):  1323-1329. 
doi: 10.3969/j.issn.1674-8115.2024.10.015

Abstract ( 42 )   HTML ( 2 )   PDF (1324KB) ( 15 )  

FOXM1 (forkhead box M1) is an important member of the FOX transcription factor family and plays a critical role in driving the progression of multiple malignancies through its transcriptional regulatory functions. Moreover, the overexpression of FOXM1 is associated with poor prognosis in many types of cancer, as it regulates a variety of biological processes such as gene expression, cell proliferation, invasion, metastasis, and apoptosis. Presently, aberrant metabolic reprogramming has been considered as the major characteristic of cancer development, determining the survival, growth, and proliferation of tumor cells. Accumulating evidence suggests that FOXM1 serves as a "bridge" between metabolism and tumorigenesis. This review aims to provide a comprehensive summary of the research progress in the relationship between FOXM1 and tumor cell metabolism, offering theoretical insights for the development of novel anti-cancer drugs targeting FOXM1.

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Case report
A case of exertional rhabdomyolysis with RYR1 gene variation
WANG Guangpu, WANG Yakun, WU Di, BAI Shoujun
2024, 44 (10):  1330-1334. 
doi: 10.3969/j.issn.1674-8115.2024.10.016

Abstract ( 31 )   HTML ( 2 )   PDF (1777KB) ( 21 )  

The etiology of rhabdomyolysis in adults is multifaceted, with one cause being physical exertion, termed exertional rhabdomyolysis (ERM). Characterized primarily by the destruction of muscle cells, ERM results in the release of intracellular contents into the bloodstream, leading to a spectrum of symptoms, including myalgia, dark urine, weakness, and marked elevations in serum creatine kinase (CK) and myoglobin levels. Some patients experience recurrent symptoms, persistently high serum CK levels (exceeding 50 times the normal upper limit), or unexplained severe manifestations. Despite this, the underlying pathogenesis remains elusive in numerous cases. Recent studies have implicated mutations in the RYR1 gene as a potential cause of exercise-induced ERM. This report describes a patient presenting with ERM and a heterozygous RYR1 gene missense mutation. Following treatment with fluid resuscitation, metabolic optimization, and antioxidant therapy, the patient exhibited clinical and biochemical improvement.

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